What I find interesting is the fact that modafinil and caffeine ranked almost the same. I've always thought it would be interesting to try modafinil because of the widely claimed cognitive benefits and how it has less drawbacks than caffeine, but if it ranks essentially the same as caffeine, there's really no point to trying it that I can see. Caffeine doesn't really do that much to be honest. It seems as though none of these really have any profound effects on mental capability.
The difference between caffeine and modafinil come down to two things for me -
- length of effect (caffeine seems to pick me up for had ran hour to an hour with a 30 min lead time - vs 12 hours with modafinil with a 45-1hr lead time)
- side effects (if I am really tired and have to get a big day out, I might end up havering somewhere between 6-12 'doses' of coffee. Cf. 200 mg modafinil- by 3/4 through the day on the caffeine track I am jittery, have a noticeable essential tremor, my eyes are gritty - all this vs nothing on modafinil- nothing for me at least)
Few notes:
Modafinil was a massive productivity booster while I was at uni. I would occasionally do a 36 hour period of solid study or work or whatever to cover a whole bunch of content and take up to 600mg modafinil durin this period, sometimes followed by a normal 8 hr sleep, then repeat. It was wonderful; I covered huge sections of my curriculum efficiently. The only side effect I have ever really felt from modafinil is a slight bit of 'coke mouth' when taking a high dose, and a minor bit of jaw clenching a la MDMA at the high doses as well.
Now I use only when work is very busy and I have been stupid with my sleep, 100mg mane for a couple of the days of the week seems to work very well although I am not an 'every day' doser and always prefer to be around 36 hours from my last dose if I am going to drink or take any other substances (I find I don't get the sensation of drunk if still on modafinil)
Edit: to more directly respond to your post, as opposed to ramble, you note that caffeine doesn't do that much to your mental capacity.
Modafinil doesn't really either. The studies that have looked at mental capacity, creativity etc whilst under modafinil cf. amphetamines cf. placebo have all shown decreasing returns for people of normal or high baseline cognitive function. Modafinil is not going to make you smarter. But if you take it in the right environment, it can make you a lot more productive
Be careful with regards to the jaw clenching. I used modafinil extensively several years ago as part of a clinical trial/research study participant. I now have stress fractures in two of my lower teeth from the jaw clenching, and will either need to eventually replace those two teeth with implants or (hopefully) stem-cell derived replacement teeth.
The body is not built for constant stressing, in many ways.
One other big difference, in my experience but also heard the same from others, is that caffeine makes it hard to sleep (like cocaine, etc.) whereas modafinil doesn't, it just makes you not think about the fact that you need to sleep. If you take modafinil too close to when you decide to go to bed you'll be able to go straight to sleep, even if the effects of the drug only just kicked in, which is very different to going to bed after drinking a couple of coffees or taking some coke, or other stimulants. (Of course, YMMV.)
By the way, what is 'coke mouth' - just a numb feeling? I've never felt anything from taking modafinil (though never used particularly high doses, or used particularly often). Don't know if 'coke mouth' is something else that I've never experienced?
Ah yes I forgot to mention the sleeping.
I've also been able to get great effects (in terms of 'recovery') by taking modafinil before bed if I only have between 1-3 hours available to sleep, then getting up and having a good productive 18 hour day. Although I dream a lot more, but I consider that a bonus.
Haha 'coke mouth' is overly chatty, will speak at length about anything. Sorry for the lingo
I'm a little skeptical about that. I wonder about having two considerations (benefits/drawbacks) apparently boiled down to one number.
I'd hazard a guess that the level of enhancement both bring are about the same for many people... but that the drawbacks of caffeine are more or less something that everybody's used to.
For me, using adrafinil to get by on less sleep was considerably more desirable than using caffeine.
Then again, the drawbacks of caffeine are strong enough for me that I generally don't use it, so I might be an outlier.
Caffeine sensitivity can drop very quickly. To me it takes about 200mg to notice much from caffeine. Maybe you've simply not tried high enough doses (be careful - caffeine withdrawal can get nasty)
I use modafinil quite regularly to defer sleep to work on projects through the night, and the difference from caffeine is very noticeable to me - to get the same effect from caffeine means jitters and noticeable increased heart rate.
Don't expect to get mental abilities above your normal rested self for either one of these. You should expect to be able to keep focusing for longer periods, including when tired, though.
More importantly to me than the immediate negative effects of caffeine is that I can take breaks from modafinil at any time, for any period of time, and feel no withdrawal. If I use large enough doses of caffeine to regularly make it through a night without sleep, and want to take a break from it, I need to step down my caffeine intake slowly or risk a week of intense headaches, diarrhoea, shakes in the evening, and fever.
-caffeine does nothing to me; I can drink a coffee in the evening and go right to sleep; I can drink water all day and have problems sleeping; It just doesn't have any effect on me at all as long as sleepiness and concentration are concerned
-when I take Moda, caffeine somehow starts having huge effect: one cup of coffee or tea even makes me focused and willing to do stuff and there is just no sleepiness regardless of how tired I am;
I am not sure if my reaction to caffeine while on Moda is what people usually feel when they drink a coffee or "energy drink" but the effect is awesome :)
Many say modafinil gives you an ability to focus deeply on things for long periods of time, which caffeine doesn't really do. The downside appears to be that the "big picture" view sometimes seems to be lost.
I'm not sure that kind of thing would show up in this survey.
Yeah.. I know this is just hearsay and anecdotal evidence.
Unless possessing prescription-only medicine is illegal where you live (doubtful), you can just order it on the internet. I don't think it's a restricted drug anywhere.
Be careful, in the country I live in (Austria) it is illegal to import prescription drugs. Customs made me pay a fine of about 60$ for trying to import Melatonin (and I didn't get the Melatonin either).
Amazing. In the US, melatonin just sits there right on the shelf where anybody who feels like can buy it for a couple bucks. No prescription, no ID, and extremely cheap.
The U.S. is somewhat idiosyncratic in classifying melatonin as not being a drug at all, but rather a dietary supplement, akin to natural/alternative-health stuff like St John's wort, fish-liver oil, or the various herbs used in traditional Chinese medicine. Therefore it doesn't even get to the prescription vs. OTC decision, since dietary supplements are basically unregulated, as long as they don't make medical claims on the label or in advertising.
There's a few reasons why Adrafinil isn't scheduled. It wasn't ever approved by the FDA or marketed in the US and never used heavily in the US, thus the DEA never bothered to regulate it. When Modafinil got FDA approval, the DEA felt the need to evaluate it.
Adrafinil was used in France and other parts of Europe, however Cephalon is no longer allowed to market the drug in France, and they have discontinued it.
What about Nicotine? Back in college and for a few years afterward, I used to put in a big fat dip (or chew) for all/late-nighters to help me buckle down, focus, and stay alert. I stopped for all the standard health reasons, but I find that caffeine is only about 2/3 as good.
Using nicotine gum, you can avoid the typical health hazards of tobacco products. I personally found that caffeine wasn't comparable to nicotine, the former just keeps me awake, while the latter can keep me focused and motivated for several hours.
Not a good idea. Nicotine gum is not too good for gingival health.
Nicotine patch is consider the safest form of nicotine delivery. Also the most expensive.
E-cigarette is a good 2nd option. Vape unflavored or menthol, because the health effects of flavorings are still out there. Vendors have mostly stopped using diacetyl in their flavorings. Diacetyl gives that vanilla aroma, but also responsible for popcorn lung.
Still they're using acetoin which could convert to diacetyl in small amount uncertain conditions. There's also the issue of vegetable glycerin (used as a carrier) converting to acrolein under high heat. I think this is a non issue if you don't let your atomizer gunk up, which inhibits heat transfer from the coil.
I'm alarmed at the ubiquitous use of aldehydes in flavorings. Most of these have no solid research proving the safety.
If money is not an issue, I would use the patch everyday instead of e-cig.
Nicotine, I've found, is the only sustainable option in the long run. Methylphenidate, amphetamines, other dopaminergics, caffeine, modafinil, they all poop out eventually.
I'm also convinced that nicotine is the safest and most effective nootropics known at the moment until cortex gets around to releasing their ampakine.
The structures of which are all under secret, so we self-experimenters can't even get it custom synthesized.
> the health effects of flavorings are still out there
This is very true. I have been very concerned with "vapers" I know buying cheap juices from China - to me this is rolling the dice, almost as bad as smoking!
You will find that reputable juice mixers will generally make statements about their ingredients. My usual favourite (indigo vapours - I have no commercial interest, just a customer) for example explicitly state that they do not use any flavour containing diacetyl, acetyl propionyl or acetoin.
Flavours which may contain aldehyde elements are a concern, but what is much more my concern with e-cigs is the long-term effect of propolene glycol inhalation, and potentially significant formaldehyde levels potentially produced by the heating and/or oxidation of the base liquids. There's a decent amount of research ongoing in these areas.
Despite these issues I am reasonably confident that e-cigarettes are within a safety range I am comfortable with if (and only if) used with high-quality liquids.
The study found variations up to 20x in levels of formaldehyde contained in the vapour produced by some top e-cigarette products. At the low range, the levels are of little concern and barely above background. At the high range, they are of some concern. Unfortunately brands, etc are not broken down.
I have a strong suspicion that formaldehyde levels correlate with country of origin and/or quality of the liquids involved. If you stick to using PG sourced from countries with reliable certification systems I think it is OK.
Is nicotine gum actually not a health risk? Tobacco held in the mouth (for example Scandinavian 'snus') certainly has serious effects with long-term use, albeit they aren't exactly the same as smoking cigarettes. Gum is generally sold for short term use, so not sure if it's actually better, or just not generally used for long enough to see the effects.
The gum poses risk to the gingival tissues. It can cause gum recession. Not to mention it also taste terrible and hard to control delivery. Chewing it too fast can leave you woozy and nauseous.
The reason I prefer nicotine over other stimulants, it's oddly relaxing and motivating at the same time.
Caffeine either leaves me jittery or anxious or it doesn't work at all after 2 weeks. There is a ton of research out there proving the positive effects of nicotine.
I've never smoked, and tried nicotine gum to experiment with the cognitive effects. I managed two pieces of gum because of the taste and delivery control before I threw the rest in the trash... Haven't gotten around to trying a patch..
The patch stops working much faster while ecig's effect never seems to wear off.
I can only assume that it is because the patch maintains a constant level of nicotine in your bloodstream causing tolerance to develop faster and it is unable to spike the nicotine concentration unlike ecig when you can take a deep drag.
Ecig gives a totally different feeling than patch. You'll definitely feel it hit when you take a long deep drag.
My understanding is that nicotine itself is not particularly carcinogenic (there are some studies indicating slight increases in tumorigenesis in conjunction with specific carcinogens, and others indicating no increases), but there are a lot of other compounds in tobacco (including chewing tobacco) that are highly carcinogenic. To my knowledge there are no studies of the carcinogenic potential of long-term nicotine replacement therapy in humans.
Nicotine has several metabolites. NNN, NNK and cotinine. The first two are carcinogenic, but the risk is negligible (but not absent) for smoking cessation therapy. The effects of cotinine appear to be slightly negative on brain health, but of course there are dietary and lifestyle factors which play into the cash value of all this.
Nicotine also appears to be slightly deleterious for kidney and heart health, so it's not entirely benign. It also has to be avoided with female oral contraceptives (greater risk with age) otherwise the risk of stroke increases fairly dramatically.
Do I use nicotine knowing these risks? Yes as a cognitive enhancer, but under the assumption that I'll cease before the age of 40 or upon financial success, while in good health and maintaining a fruit and vegetable rich diet.
> It only takes a few days of use for signs of addiction to show.
Eh... not for me. I can use caffeine for days and then not use it for days no problems at all. Of course probably because caffeine does absolutely nothing to me. I just like the hot beverage.
I think a better way to deal with the placebo affect is to only look at accounts where usage is greater than ninety days. As my psychopharmacologist put it, "you can cure just about anything for four weeks with a sugar pill."
Some proponents of alternative medicine have claimed that coffee enemas have an anti-cancer effect by "detoxifying" metabolic products of tumors.[4] There is no medical scientific evidence to support any anti-cancer effect of coffee enemas.[2][5][6]
Coffee enemas can cause numerous side effects, including infections, sepsis (including campylobacter sepsis), severe electrolyte imbalance, colitis, polymicrobial enteric septicemia, proctocolitis, salmonella, brain abscess, and heart failure.[4][6][7][8][9][10][11][12][13] If the coffee is inserted too quickly or is too hot, it could cause internal burning[14] or rectal perforation.[15] Long term use of coffee enemas can lead to malabsorption of fat, fat-soluble vitamins, and calcium.
The use of coffee enemas has led to several deaths as a result of severe electrolyte imbalance, hyponatremia, dehydration, pleural and pericardial effusions.[8][16] The U.S. Food and Drug Administration (FDA) has ruled that study participants must be warned of the risk of death from coffee enemas in studies that use them.[17][18]
I've been taking modafinil for a while now (over a year). I initially started taking it to help with a massive workload at my job. I was a long-time software engineer at Google at the time. I was utterly burned out and couldn't retain my focus for more than 10-15 minutes- definitely not enough when you're writing c++ code and need to retain a huge amount of state in your head (header file definitions, pointer ownership, etc. etc.). But i wasn't in a situation where i could immediately take time off or change jobs/groups. So i started taking Modafinil to see if it would help me concentrate and get things done.
The immediate benefit and the thing that i still love it for today is how focused it makes me. As a programmer, most of my day is just getting things typed out. Pure creative thinking is maybe 1 hour a day at best. Without modafinil, if people came and interrupted me, i would get distracted, surf the web and it could easily take me upto an hour to get my head back in the code (especially since i hated what i was doing). With Modafinil, i would just retain stuff and be able to get back to work immediately. I'm in my mid-30s. Even on a good day, without Modafinil, i could stay in flow for maybe an hour or so before i would get distracted and lose focus. On Modafinil, 3 hours is average, 4 hours happens sometimes.
You know when you're fixing bugs in a big codebase and for each bug you kind of have to load up state in your head and think -oh yeah i need to change x,y,z here and a,b,c there and these tests 1,2,3 have to change and i should probably make sure foo and bar are still working. Well with modafinil i was able to think of that and keep all of it in my head for the 2-3 hours it would take me to type out a fix. Or you're reading a few bug reports and you are working on fixing one - you look at the file you're in and realize that while you're working in that file you could fix 2 or 3 other things or you could do a refactor - and you just do it without losing state in your head of where you are in the original bug. Modafinil let me do that- it was totally like a ram upgrade. (Or really like i wasn't burned out or was 25 again or something).
So yeah my short-term recall also went up. Another example - at google we had lots of command line tools each with tons of options. It used to be a real mental effort for me to recall the 8-10 options i would have to pass on the command-line along with gigantic path and filenames to get something simple done. This isn't uncommon- some of the most popular internal webpages are commandline option references for the really common tools. And it was a huge distraction - to have to drop what you're doing to have to go to some webpage, scroll around or click find until you found some poorly documented option that maybe did what you wanted etc. With Modafinil, that was all just in my head for the whole day - enough so that at the end of the day i could make up shell scripts for the useful stuff, but during the day i could work really fast because i wasn't looking stuff up all the time.
So yeah it did great things for me. But the bad news- i tried taking it every day - after a week, paranoia set in and mood swings. I would get extremely defensive about simple comments in code reviews. Typically i would take 200mg only in the morning so i could sleep at night- but if my schedule was bad and i went more than 3-4 days without sleep i would start having persistent hallucinations that lasted 10-15 seconds - not just corner of the eye stuff but talking to people who weren't there.
Nowadays, i take it at most 100 mg at a time a maximum of twice a week. I really enjoy programming and i want to think i'm good at it so taking Modafinil felt a little like cheating with steroids or something. My current job is much easier than Google and I've been able to replace most of the positive effects of Moda by doing a ton more planning - e.g. i help my short term memory by writing copious comments, keeping a detailed log of exactly what i'm doing in org-mode, exercising good email discipline, writing code much more defensively so i don't actually keep a lot of state in my head etc. etc. I meditate every day even for 5 minutes just in case that will help with focus. A lot of this works really well. But if the shit hits the fan at work and I'm debugging blind in a bunch of crappy code i've never seen before, or my fragile ego requires I be the guy who is just faster than others and gets stuff done, that's when i still reach for Modafinil.
Did you ever try to take naps and compare the effects to taking Modafinil? I nap about for about 20-40 minutes right after lunch and have a RedBull immediately before laying down.
I'm quite surprised to see caffeine ranked so close to modafinil. I've never used modafinil but from what I've read, for some people it's almost a wonder-drug. Caffeine gets me "high" but if anything, it can even be counter-productive at times. I wouldn't rate it anywhere near life-changing.
I took modafinil in the form of Provigil. Wasn't very similar to caffeine. It's more akin to Adderall. However, I still rank caffeine as more productive for me than either Provigil or Adderall. Provigil was weird, seemed to increase my hearing, and put me on edge. I was certainly more alert, but to an extent that was just excessive. I'd pay attention to so many trivial details that it was mentally and physically exhausting me. Things I never noticed before, song lyrics, instruments in songs, people's mannerisms, etc.
Adderall wasn't as bad, but it just wrecked my physical state. Twitchy, nervous, jaw hurt, wouldn't eat. In low enough doses, adderall is probably as useful as a cup of coffee. Long term health risks though seem pretty bleak.
Wellbutrin is another wonder drug that's not always talked about. Increased my concentration, increased my sex drive, increased my athletic performance... But! The first week on a full dose and I wanted jump through a window. Does very weird things to your brain (epileptic seizures included). I described it as being able to feel things in my head that I shouldn't be able to. Started hearing lots of high pitched humming. Apparently all side effects, bleg.
I have always had issues that are consistent with low-to-moderate ADD (never bothered getting diagnosed) and caffeine provides a noticeable, but not drastic, improvement for me. I've never tried any other drugs.
It is probably safe to say the effectiveness of caffeine/modafinil/adderall depends on your unique personality, brain chemistry, etc.
Well. I have tried modafanil from two different sources (both were modalert iirc) and noticed absolutely nothing. I tried various doses. I tried taking it before staying up all night and after. Each time was a complete disappointment. So it could be hype, me being unlucky with fake pills or differences in physiology.
Same thing here. I was thrilled to learn it could be prescribed for sleep apnea and was provided with free samples. I felt nothing. An acquaintance mentioned it did wonders for resetting the internal clock when traveling to different time zones, I'll try it again when that occurs.
The definition of nootropics used here excludes them (too many adverse health effects), but I wonder how the drugs on this list compare to e.g. amphetamines in terms of pro-productivity effects.
The problem with amphetamine is, when they do work, the crash is horrible. When the crash goes away, it no longer does anything. So you have to up the dose and the cycle starts again. Some people use NMDA antagonist to reverse tolerance, but lets just say that they do a lot more than reverse your tolerance.
In the end, most user end up with a permanent tolerance that no amount of drug vacation will lower.
I'm not even mentioning here the whole issue of amphetamine disrupting vesicle pH gradient, causing dopamine leakage. Dopamine is very prone is auto-oxidation to quinone when they float free around in the cytosol.
The disruption of the pH gradient is the central part of amphetamine's mechanism of action. Dopamine is stored inside vesicles inside presynaptic neurons. By disrupting the proton gradient between the lipid bilayer of these vesicles, dopamine is allowed to leak out and released into the synaptic cleft.
Which is part of the reason why amphetamine increases extracellular dopamine. Unfortunately, instead of being nicely packaged in vesicles, now some of these dopamine are floating around in the cytosol, making them susceptible to autooxidation to quinones, nasty stuff.
Unfortunately, most of these research are behind paywall but that is the little lf what I remembered from all the reading years ago.
Another related danger of amphetamines: because they make you feel good, they create a dopaminergic illusion of proficiency. Whether or not they are actually improving your proficiency can be difficult to judge.
>One of the nootropics measured, choline bitartrate, has carefully regulated ability to cross the blood-brain barrier beyond a certain level, and so it would be surprising if it had direct and immediate cognitive effects.
This isn't quite right. This is true of choline bitartrate itself, but IIRC it is fairly quickly metabolized into other forms of choline that can cross the BBB.
I would say it's pretty likely that increasing choline intake would have a significant effect on cognition. Humans have been consuming large amounts of fish for much of our evolutionary history, compared to today's typical diet. Given the way choline is used by our brains, and the relative plethora we had available when our brains were evolving, it's hard to believe that we get as much as we can use in a modern diet.
I have a fair bit of experience with modafinil/adronafinil, so if anyone has any questions, feel free to ask. I'm not recommending trying them without docter's prescription, of course.
It helped me greatly to stay up longer, to sleep less, and to concentrate better. However, those effects get much weaker over time: the sleep effects for me were less clear after 1-2 months, the concentration after weeks. Side effects can be nasty though, including limited appetite and gastrointestinal discomfort.
For the rest of the list: I've also tried various -racetam's, and they did nothing for me. Creatine, vitamin D don't have nootropic effects for me (but I still take them for other reasons). Caffeine is meh. Haven't tried the rest of the list.
Would love to hear your general thoughts on Modafinil. One of the things they say is that it has minor side-effects and that tolerance builds up really slow, if at all, in comparison. What's your take on it, empirically?
First a warning, because I've seen many misconceptions: Modafinil is not a sleep replacement. Especially not long-term. Do not use it that way. Its anti-sleep property is that it suppresses many parts of the urge to sleep. It does not provide any of the effects sleep provides.
--
Well, I've always had issues with sleep: I have an 25 hour circadian rythm, so before modafinil I often just let it run and wake up an hour later every day. I thought modafinil might be something useful to help me experiment with my sleep. Note that I did not get a doctor's receipt, so I imported the drug myself. (I'm not in the US; it's not a felony where I am.)
You say "in comparison"-- I must say that I do not have much to compare it to. The only other substance of this kind that I feel an effect of is caffeine, and it's on a completely different level, in all ways.
Side-effects I noticed were mostly dry/chapped lips, reduced appetite and diarrhea-- the last of which seems not to be very common.
In terms of its nootropic effects, I'm normally very bad at focusing on stuff for long periods of time, and for some periods it helped me focus for long times on tedious things. Or it helped me focus on cleaning the house really well, reading the internet thoroughly and avoiding what I had to get done. But if I used it and spent a night studying, I would remember the material studied very well. This concentration effect was also the quickest to fade after longer use.
The main effect is its anti-sleep property is that it suppresses many parts of the urge to sleep. It does not provide any of the effects sleep provides.
Right now I don't use it, because I am not working on anything that would benefit from it, and the side effects are not worth it to me right now. Also, melatonin has helped me with my sleep rythm issues for some time, so I don't need it for that.
I did not notice any addictive effects whatsoever. There's no high you get from it, nor a low after you stop, perhaps besides sleeping a bit longer for a few days.
I recall reading that unusually-timed melatonin supplementation worked for at least one person.
From HPMOR notes:
>Around a year ago, some friends of mine cofounded MetaMed, intended to provide high-grade analysis of the medical literature for people with solution-resistant medical problems. (I.e. their people know Bayesian statistics and don’t automatically believe every paper that claims to be ‘statistically significant’ – in a world where only 20-30% of studies replicate, they not only search the literature, but try to figure out what’s actually true.) MetaMed offered to demonstrate by tackling the problem of my ever-advancing sleep cycle.
Here’s some of the things I’ve previously tried:
Taking low-dose melatonin 1-2 hours before bedtime
Using timed-release melatonin
Installing red lights (blue light tells your brain not to start making melatonin)
Using blue-blocking sunglasses after sunset
Wearing earplugs
Using a sleep mask
Watching the sunrise
Watching the sunset
Blocking out all light from the windows in my bedroom using aluminum foil, then lining the door-edges with foam to prevent light from slipping in the cracks, so I wouldn’t have to use a sleep mask
Spending a total of ~$2200 on three different mattresses (I cannot afford the high-end stuff, so I tried several mid-end ones)
Trying 4 different pillows, including memory foam, and finally settling on a folded picnic blanket stuffed into a pillowcase (everything else was too thick)
Putting 2 humidifiers in my room, a warm humidifier and a cold humidifier, in case dryness was causing my nose to stuff up and thereby diminish sleep quality
Buying an auto-adjusting CPAP machine for $650 off Craigslist in case I had sleep apnea. ($650 is half the price of the sleep study required to determine if you need a CPAP machine.)
Taking modafinil and R-modafinil.
Buying a gradual-light-intensity-increasing, sun alarm clock for ~$150
Not all of this was futile – I kept the darkened room, the humidifiers, the red lights, the earplugs, and one of the mattresses; and continued taking the low-dose and time-release melatonin. But that didn’t prevent my sleep cycle from advancing 3 hours per week (until my bedtime was after sunrise, whereupon I would lose several days to staying awake until sunset, after which my sleep cycle began slowly advancing again).
MetaMed produced a long summary of extant research on non-24 sleep disorder, which I skimmed, and concluded by saying that – based on how the nadir of body temperature varies for people with non-24 sleep disorder and what this implied about my circadian rhythm – their best suggestion, although it had little or no clinical backing, was that I should take my low-dose melatonin 5-7 hours before bedtime, instead of 1-2 hours, a recommendation which I’d never heard anywhere before.
And it worked.
I can’t #&$ing believe that #$%ing worked.
(EDIT in response to reader questions: ”Low-dose” melatonin is 200microgram (mcg) = 0.2 mg. Currently I’m taking 0.2mg 5.5hr in advance, and taking 1mg timed-release just before closing my eyes to sleep. However, I worked up to that over time – I started out just taking 0.3mg total, and I would recommend to anyone else that they start at 0.2mg.)
It's a very subjective question. Modafinil makes me feel Not Tired. That's pretty much it. Not amped up, not hyper focused, just very awake. If you're having trouble focusing because your tired then this is a huge improvement. But I don't think it's much better than just being actually well rested.
Tolerance didn't seem like a huge issue, but I also wasn't taking it every day.
Tolerance does happen with modafinil, but sensitivity increases again very rapidly for most people, so if you don't take it every day you might never start noticing it.
FYI: I would strongly suggest getting a RX for Modafinil (Provigil) and not Nuvigil (Amodifinil). Nuvigil is very expensive and my insurance company required a whole battery of additional tests before they paid for it. I believe Modafinil is now generic so I imagine they care much less.
Last time I checked, cephalon had some sort shady deal to keep generic modafinil off the market for a few more years (paying generic manufacturers to not bring it to market). If modafinil goes generic, it will be really good news.
From what I've heard before, it was almost impossible for people to get approved by insurance for modafinil, maybe times have changed and I need to pay the doctor a visit in the future.
I have an actual sleep disorder and I am currently going through hell trying to get my insurance to pay for modafinil, and I've been through the whole battery of tests. :( I don't want to be "smarter" I want to be awake.
I think you have to have certain conditions for nootropics to really do anything.
I take Aniracetam and it makes a big difference in my life. I take a LOT less than most people, and the thing I notice is that I don't have songs stuck in my head.
This may seem like a weird condition to be trying to get rid of but it makes a huge difference in my life and my concentration. There may be other effects, and some fuzzy metrics we could test for like how well I do at Baby Animal Match, or how fast I can do a Sudoku, but I can "observe" this one in my day to day life.
I've been following this topic for 20-30 years and this is the only supplement I've taken where I've felt mental state changes. Its a noticeable anxiolytic. If its not a strong one, I can only wonder at what a real strong one must feel like.
Not feeling "performance anxiety" most likely does improve performance for most people.
Where you obtain this stuff is a mystery. Amazon used to ship it, but it appears and disappears. One interesting problem is what is merely OTC in one country is prescription only in another country. This is typical for all the substances in the list. This is typical for most substances, it seems, like stevia and perhaps a hundred food dyes.
Stuff I've tried with no measurable performance gain: caffeine, piracetam (headache), creatine, vinpocetine, choline, some others. Other than occasional headache, not much effect one way or the other.
You can find bulk powder but I find the taste unbearable. Rx aniracetam is far too expensive. I'm just waiting for the day when cortex gets their high-impact ampakine onto the market.
I was really surprised at the effect of aniracetam also. Usually most of these nootropics either do nothing or they jack up your heart-rate like any other stimulants. It's interesting to note that aniracetam is considered an ampakine, which lowers the threshold required for long-term potentiation.
When I was taking aniracetam, the anxiolytic effect was too strong to be placebo. Almost as strong as alcohol. I was genuinely surprised. It makes activities like staring at leaves fluttering almost magical.
Eventually I gave it up because this effect wore off and it was too expensive.
Just to let everyone know, a very very rare but very serious side effect of modafinil is Stevens–Johnson syndrome and other potential life threating skin conditions.
What makes people believe that their brains are not good enough just as they are? If you take nootropics you're messing with the most precious mechanism of your body. Are there any studies at all about the effects of long-term use on perfecly healthy young people?
I wish they'd included amphetamines (both ADHD medications like adderall/amphetamine and more serious things like desoxyn/methamphetamine), for comparison.
Okay, I have read the fine blog post (which took a while to load). The article leads off by defining nootropics as "substances which purportedly improve mental functioning with relatively few side effects when used responsibility."
The blog post author mentions a few small-n, limited duration studies, and then describes his voluntary-response survey methodology:
"I asked people in the two largest online nootropics communities (that I know of), Reddit’s r/nootropics and Longecity’s Brain Health forum, to take a survey describing their use of 31 different substances. I got 162 responses."
"Respondents were asked to rate their subjective experiences of different nootropics on a scale of zero (completely useless, did nothing) to ten (life-changing). Comments on Reddit suggest several people misunderstood the scale, but not much I can do about that at this point."
So all the data here are voluntary-response data, with the known problem of response bias[1] and other defects about which I have an entire FAQ[2] I post on HN from time to time. Worse than that, all the data are self-report data,[3] which also have plenty of problems, even when gathered in a comprehensive survey with a representative sample of the general population, because of the risks of incorrect self-reports unless checked by other data sources that are objective.[4]
The blog post author then gives a lengthy description, with pretty colored charts, of his hand-waving statistical analysis of these dubious voluntary reponse, self-report data. It would not be wise (that is, it would not be a sign of improved mental functioning) to take these conclusions seriously as a description of how nootropics work, or indeed if they work at all. The author would do well to study fundamental principles of statistics by reading the online articles "Advice to Mathematics Teachers on Evaluating Introductory Statistics Textbooks"[5] and "The Introductory Statistics Course: A Ptolemaic Curriculum?"[6] to wrap his mind around how strictly necessary it is to have a valid data-gathering plan before engaging in any statistical manipulation of the data. Garbage in, garbage out. More background on experiment design to think about while evaluating the blog post kindly submitted here can be found in the essay "Warning Signs in Experimental Design and Interpretation"[7] by Peter Norvig, LISP hacker and director of research at Google, on how to interpret scientific research.
What might big-time convince me to try out a nootropic substance would be an objective demonstration that someone with typical abilities (say, someone who goes into online discussion with a known propensity to believe what's on Reddit without checking it) can become a person with thoughtful insight (say, someone like Peter Norvig) at adult age simply by ingesting the nootropic. On my part, I like to improve mental functioning with relatively few side effects as much as anybody here, and one way I attempt to do that in middle age is by reading thoughtful articles by careful scholars and then discussing those among the learned participants on Hacker News. I'd appreciate comments from any of you about how one could know, objectively and verifiably, that a nootropic substance really does people good (even if they don't feel that themselves). I especially invite comments from participants here who have a professional understanding of statistical studies in clinical trials of new medicines.
Medical progress often starts with observations, and is confirmed by trials. Penicillin is one such example.
To discount the value of observations is to ignore an important part of the discovery process.
There is extremely limited data available around the use of nootropics for mind enhancement (as opposed to in medical use for treating illness). In the absence of of such data a survey like this indicates that there are a few things worth studying in more depth (and some supposed nootropics that seem worthless).
The author appears extremely aware of the problems with their methodology, and makes no attempts to hide these problems. To pull quotes:
The online nootropics community consists of mostly healthy individuals looking to use these substances to gain motivation or clearer thinking. They tend to “outpace” the scientific literature, using some substances that haven’t yet been shown to work, or haven’t been shown to benefit healthy individuals.
...
" I would have liked to have some placebo nootropics to use as a comparison, but since I wasn’t running a trial, I didn’t have that option. I did, however, try to assess the placebo effect in a couple of sneaky ways."
...
"I have very low confidence that these represent real effects rather than artifacts of the gymnastics I had to do to make the data correlatable at all, and I report them only to encourage other people to do more sober analyses."
I think attempting to do this - knowing that people will criticize the methodology - is admirable.
Observations are one thing, attempts to do any kind of serious study on the results are another. It is not meaningful to do statistics on data that bad.
No at all - you just need to be careful what conclusions we draw.
We can safely report the statistic that "more people self report caffeine having an impact than ginseng."
The author goes as far as noting how many people are reporting an impact where there appears to be no known mechanism that impact could be occurring. That's a defensible statistic too.
I believe the author of this piece is keenly aware of the issues inherent to study designs such as this, which is why he discusses the methodological issues in this post. He has discussed methodological issues at length in previous posts (he is a psychiatry resident, and one who frequently goes back and addresses the primary literature) and that is taken as context to his regular readers, explaining why he doesn't devote more time to disclaimers.
Your exhortation that he should spend more time on basic understanding of statistics is misplaced, because he understands these issues, but he has different philosophical views than you on how information should be gathered and processed. Specifically, it seems to be your view that information received with noise and bias should be given (literally) zero weight, that information should be ignored unless it comes in the form of peer-reviewed, random controlled clinical trials. His philosophical view is that all information should be given some appropriate weight, and that the costs to acquire information are relevant. Random, controlled clinical trials are costly, and so we will never have them on a variety of topics of interest to us. To account for this finiteness of resources, and to suggest which areas could be more fruitful for future formal trials, it seems wise to acquire that information which can be cheaply had. This is an attempt to gather that information.
What kind of response bias are you expecting here and how would you fix it?
I mean, obviously there is a bias in favor of people who use more nootropics and find nootropics more effective. But since all I was doing was ranking nootropics relative to one another, that should mostly cancel out. I'm not sure why respondents would, for example, be expected to be a group disproportionately likely to have a stronger response to modafinil relative to bacopa compared to the general population.
More pressingly, I'm not sure how I can avoid it besides gathering hundreds of people together and forcing them to try nootropics one by one in controlled conditions, for which I don't have the resources. Even professional studies that select their subjects ahead of time have atrociously high dropout rates. If you have an implementable idea for avoiding response bias on next year's survey I'm happy to go ahead with it, but "not collect any survey data at all because available methodology isn't perfect" seems strictly inferior.
I feel like I hedged myself pretty appropriately: " we can't get good data without way more effort and resources than anyone is willing to put in, but if we ran a survey we could at least get better anecdata", "This survey does not intend to rectify [the confusion as to whether nootropics work at all]", "a pessimist might say that [this is] extracting patterns from random noise", et cetera. But given the choice between giving up because it wasn't perfect and going ahead with hedges, I figured I might as well go ahead.
Scott is well aware of all those issues. Something is, however, generally better than nothing. This is not a randomised clinical trial, not even close. It's not even a longitudinal correlational study. It's an opt in survey with a small sample. Unless you get huge effect sizes you're going to be have low certainty of anything and all it's really useful for is suggesting things for people to try or treatments to be prioritised for testing in higher powered studies.
I especially invite comments from participants here who have a professional understanding of statistical studies in clinical trials of new medicines.
Scott has an M.D. and is currently doing his residency in psychiatry.
The author would do well to study fundamental principles of statistics...
If only the author understood this. Then he might have written this in the fifth paragraph: "They tend to “outpace” the scientific literature, using some substances that haven’t yet been shown to work...people combine a bewildering variety of chemicals without being sure which ones work better than others or even whether any of them work at all.
This survey does not intend to rectify this state of affairs"
He might also have written in the conclusion: "Overall I was not too impressed with the results of this survey. No unexpected substances jumped out as promising, there was a very wide distribution from “useless” to “life-changing” in nearly everything except the -afinils, and it was very hard to find much of a dose-response relationship anywhere."
"Other goals for the future are to drag people kicking and screaming into reading directions so I know everyone’s rating off the same scale..."
Not every blog post needs to rise to the level of double blind clinical trial.
Sounds to me more like a justification for presenting useless statistics and allowing 'outpacers' to give themselves more confirmation bias (which those communities already provide in spades).
> What might big-time convince me to try out a nootropic substance would be an objective demonstration that someone with typical abilities (say, someone who goes into online discussion with a known propensity to believe what's on Reddit without checking it) can become a person with thoughtful insight (say, someone like Peter Norvig) at adult age simply by ingesting the nootropic.
I note that Norvig is a really high bar, and that reading and discussing articles is not going to have that level of effect either. (Though what effect it does have, comes at less risk.)
Many people claim that taking modafinil allows them to lose a night's sleep and feel fine the next day. It seems unlikely that they'd be so completely wrong that modafinil is not doing them any short-term good at all. Like, the typical response to "lose a night's sleep" is "have a really obviously bad day tomorrow". It would be difficult for modafinil to make someone so totally oblivious, to their own performance and the comments of people around them, as to not notice this happening.
If modafinil didn't have any clinical studies backing it up, the anecdotal evidence would be enough to convince me with high probability that modafinil has short-term benefits for many people.
I think you're missing some context here. The survey was only supposed to be better than the anecdotes that were accumulating previously. Solicited head to head anecdotes are better than unsolicited anecdotes without comparisons.
I get the impression that he's looking for information that has a well-defined objective measurement (e.g. performance at some standardized task), and is not subject to the selection and survivorship biases of voluntary response data or the biases inherent in subjective responses to questions about subjective experiences, when that experience can be influenced by the subject's expectations.
